Complement has been considered to be mediator of humoral immunity active in antibody-mediated lysis of bacteria and cells, and in anaphylactic and Arthus reactions. It has been largely ignored as a potential mediator of cellular-immunity. The discovery that tissues and cells of the reticuloendothelial system syntesize complement proteins and that lymphocytes, monocytes, and polymorphonuclear neutrophils possess cellular membrane receptors for complement proteins, clearly suggests the need for studies to determine whether complement plays a role in cellular-immunity. It is the objective of the present proposal to provide the basic information necessary for such functional analyses. The applicant has recently reported the finding of neoantigenic-markers for the membrane attack complex of complement on lymphocytes. The complement membrane attack complex is a macromolecular complex C5b, C6, C7, C8 and C9 which induces irreversible membrane changes, osmotic swelling and lysis of cells. The studies outlined in the present proposal will seek to answer three questions: First, are C5, C6, C7, C8 or C9 present on the surface of peripheral blood lymphocytes? Second, does C5, C6, C7, C8 or C9 singly (or in combination) bind to the lymphocyte membrane, i.e. do receptors exist for terminal complement proteins? Third, do lymphocytes synthesize C5, C6, C7, C8 or C9 during culture and is biosynthesis under immunological control. The methods used to answer the questions will include: immunofluoresence microscopy, cell-surface radiolabeling techniques, binding reactions with radiolabeled complement proteins, metabolic radiolabeling techniques, and hemolytic assays. These studies are made possible by the recent development of methods which allow the routine purification of complement proteins and production of monospecific antisera to these proteins.